Rapid antimicrobial susceptibility testing from positive blood cultures based on Stimulated Raman Scattering Imaging analysis

The existing identification (ID) and antimicrobial susceptibility testing (AST) method requires at least two to three days to detect blood infection, and a fast and accurate detection method is very necessary for sepsis patients or Intensive Care Unit (ICU) patients. Here, we describe a direct isolated bacteria from a positive blood culture bottle (PBCB), and rapid AST method by femtosecond stimulated Raman scattering (SRS) imaging of deuterium oxide (D2O) metabolism, which can determine the antimicrobial susceptibility of bacteria from PBCB in 5-6 hours. The positive blood culture sample is passed through a filter membrane and mixed with cell lysis, after through the centrifugal which can directly isolated bacterium in order to identification by matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry (MALDI-TOF MS), following by antibiotic susceptibility testing by SRS imaging within a day. Overall, this rapid and rapid process combination of MALDI-TOF MS and SRS imaging of deuterium oxide (D2O) metabolism can solve the direct identification and antibiotic susceptibility testing of pathogen in positive blood cultures

Influence of the IGFBP3-202A/C Gene Polymorphism on Clinical Features and Surgery Outcome in Acromegalic Patients

Purpose: Excess growth hormone (GH) secretion in acromegaly patients results in increased levels of IGF-1 expression, which causes the clinical manifestations of acromegaly. IGF-1 levels are attenuated by IGFBP3, and a polymorphism in the promoter of IGFBP3 is known to affect the circulating level of IGFBP3 protein. The aim of the study was to evaluate the association of the IGFBP3 gene polymorphism with clinical features and surgery outcomes in acromegaly. We also investigate the difference in IGFBP3 polymorphism between acromegaly and general population.Methods: The study included 102 acromegalic patients and 142 sex- and age-matched healthy controls. The genotyping of IGFBP3 was carried out using the MassARRAY method. Patients were followed up for 4–12 months to estimate the neurosurgical effects. Clinical data were obtained from the medical records.Results: The CC genotype, which is associated with decreased IGFBP3 levels, was less common in acromegaly patients than among the healthy controls; although, this correlation was not significant (P = 0.056). There was no association of the IGFBP3 gene polymorphism with glucose, lipid, phosphorus, blood urea nitrogen, creatinine or uric acid levels. Additionally, there was no association between tumor size, texture, or hemorrhage/cyst, except there was a trend that more patients with the C allele (P = 0.054) needed additional treatment post-operation than did patients carrying the A allele (OR 1.985, 95% CI 0.983–4.008). Moreover, higher IGF-1 values after treatment were observed in patients carrying the C allele (P = 0.012 and P = 0.014 according to the additive model and dominant model, respectively).Conclusion: Polymorphisms in IGFBP3 may not influence metabolic parameters or pituitary tumor characteristics in acromegalic patients, but they may be associated with the hormone levels and surgery effects

Upregulation of miR-196b Confers a Poor Prognosis in Glioblastoma Patients via Inducing a Proliferative Phenotype

PURPOSE: To explore the expression pattern, prognostic value and functional role of miR-196b in glioblastoma (GBM) patients using large cohorts. EXPERIMENTAL DESIGN: MiR-196b expression was measured using the Human v2.0 miRNA Expression BeadChip (Illumina) in 198 frozen glioma tissues. The expression levels of miR-196b were also validated in an independent cohort containing 128 formalin-fixed paraffin-embedded (FFPE) glioma samples using qRT-PCR. The presence of other molecular prognostic indicators was assessed centrally in the glioma samples. Whole genome gene profiling was performed to investigate the underlying biological behavior. MiR-196b functional analyses were performed in U87 and U251 cell lines. RESULTS: The expression levels of miR-196b were inversely correlated with overall survival in GBM patients. Gene set enrichment analysis (GSEA) showed that the gene sets relating to cell cycle were significantly enriched in the cases with miR-196b overexpression. Functional analyses in U87 and U251 cells revealed that miR-196b was involved in cell proliferation. CONCLUSIONS: MiR-196b is overexpressed and confers a poor prognosis via promoting cellular proliferation in GBM patients

Rapid antimicrobial susceptibility testing from positive blood cultures based on Stimulated Raman Scattering Imaging analysis

The existing identification (ID) and antimicrobial susceptibility testing (AST) method requires at least two to three days to detect blood infection, and a fast and accurate detection method is very necessary for sepsis patients or Intensive Care Unit (ICU) patients. Here, we describe a direct isolated bacteria from a positive blood culture bottle (PBCB), and rapid AST method by femtosecond stimulated Raman scattering (SRS) imaging of deuterium oxide (D2O) metabolism, which can determine the antimicrobial susceptibility of bacteria from PBCB in 5-6 hours. The positive blood culture sample is passed through a filter membrane and mixed with cell lysis, after through the centrifugal which can directly isolated bacterium in order to identification by matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry (MALDI-TOF MS), following by antibiotic susceptibility testing by SRS imaging within a day. Overall, this rapid and rapid process combination of MALDI-TOF MS and SRS imaging of deuterium oxide (D2O) metabolism can solve the direct identification and antibiotic susceptibility testing of pathogen in positive blood cultures

Evaluation of a micro/nanofluidic chip platform for the high-throughput detection of bacteria and their antibiotic resistance genes in post-neurosurgical meningitis

Background: Post-neurosurgical meningitis (PNM) is one of the most severe hospital-acquired infections worldwide, and a large number of pathogens, especially those possessing multi-resistance genes, are related to these infections. Existing methods for detecting bacteria and measuring their response to antibiotics lack sensitivity and stability, and laboratory-based detection methods are inconvenient, requiring at least 24 h to complete. Rapid identification of bacteria and the determination of their susceptibility to antibiotics are urgently needed, in order to combat the emergence of multi-resistant bacterial strains. Methods: This study evaluated a novel, fast, and easy-to-use micro/nanofluidic chip platform (MNCP), which overcomes the difficulties of diagnosing bacterial infections in neurosurgery. This platform can identify 10 genus or species targets and 13 genetic resistance determinants within 1 h, and it is very simple to operate.A total of 108 bacterium-containing cerebrospinal fluid (CSF) cultures were tested using the MNCP for the identification of bacteria and determinants of genetic resistance. The results were compared to those obtained with conventional identification and antimicrobial susceptibility testing methods. Results: For the 108 CSF cultures, the concordance rate between the MNCP and the conventional identification method was 94.44%; six species attained 100% consistency. For the production of carbapenemase- and extended-spectrum beta-lactamase (ESBL)-related antibiotic resistance genes, both the sensitivity and specificity of the MNCP tests were high (>90.0%) and could fully meet the requirements of clinical diagnosis. Conclusions: The MNCP is fast, accurate, and easy to use, and has great clinical potential in the treatment of post-neurosurgical meningitis. Keywords: MNCP, PNM, Identification, Drug resistance gen

Serum amyloid A: A new potential serum marker correlated with the stage of breast cancer

Previous studies reported that serum amyloid A (SAA) is elevated in patients with tumors, including breast cancer, compared to healthy controls. In addition, the levels of SAA increase gradually with tumor progression. In this study, we investigated the blood SAA level of breast cancer patients, and evaluated its potential as a serum biomarker for the early diagnosis of breast cancer and as a staging estimate. SAA protein was determined by enzyme-linked immunosorbent assay in serum samples from 30 healthy women, 21 women with benign diseases and 118 breast cancer patients who were subdivided into 4 groups based on their clinical characteristics. SAA levels were not statistically different in stage I breast cancer patients compared with the healthy controls and benign breast disease patients. SAA concentrations had medians of 0.63 µg/ml in normal healthy women, 0.76 µg/ml in patients with benign disease (p>0.05) and 0.82 µg/ml in stage I breast cancer patients (p>0.05). By contrast, SAA values in stage Ⅱ, Ⅲ and Ⅳ patients had a significantly higher median compared to those of the healthy, benign breast diseases and stage I groups (p<0.05). Breast cancer patients with lymph node (LN) metastasis or distant metastasis were found to have significantly higher SAA concentrations than those without metastases. SAA is not a suitable marker for early breast cancer diagnosis, but its level is correlated with the stage of breast cancer. Thus, it may be a good candidate marker for the staging and prognosis of breast cancer

Association between acromegaly and a single nucleotide polymorphism (rs2854744) in the IGFBP3 gene

Abstract Background It has been reported that the single nucleotide polymorphism (SNP) rs2854744 at the − 202 locus of insulin-like growth factor binding protein-3 (IGFBP3) is associated with serum levels and a number of malignancies. However, the effect of IGFBP3 gene polymorphism on acromegaly is less clear. Therefore, in the current study, we aimed to investigate whether the −202A/C polymorphism of IGFBP3 constitutes a risk factor for acromegaly. Methods The study included 102 acromegalic patients and 143 control subjects in Beijing Tiantan Hospital. The genotyping of IGFBP3 was carried out using the MassARRAY method. Serum IGFBP3 concentrations were also determined. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to evaluate the associations of genetic polymorphisms with the development of acromegaly and its different subtypes. Results The study revealed that the C allele of rs2854744 was associated with a reduced risk of acromegaly (OR 0.594, 95% CI 0.388–0.909), as well as with the female (OR 0.385, 95% CI 0.206–0.72), macroadenoma (OR 0.557, 95% CI 0.347–0.893) and monotherapy (OR 0.512, 95% CI 0.316–0.828) subgroups under the additive model. A higher serum IGFBP3 level was observed in patients with the AA genotype, but this difference was not significant (P = 0.331). Conclusion This study is one of the first to show that the IGFBP3 polymorphism may have an influence on serum levels and that the C allele of rs2854744 is associated with a reduced risk of acromegaly. This correlation was more prominent in females, those with large tumours and those treated with monotherapy in a Chinese population. Genetic polymorphism of IGFBP3 may be involved in the development of acromegaly

Association between paraoxonase gene and stroke in the Han Chinese population

Abstract Background The human paraoxonase (PON) gene family has three isoforms: PON1, PON2 and PON3. These genes are implicated as potential risk factors of cerebrovascular disease and can prevent oxidative modification of low-density lipoproteins and atherosclerosis. This study evaluated the association between the genetic variants of all three PON genes and the risks of total stroke, ischemic stroke and hemorrhagic stroke in the Han Chinese population. Methods A total of 1016 subjects were recruited, including 508 healthy controls and 498 patients (328 with ischemic stroke and 170 with hemorrhagic stroke). A total of 11 single nucleotide polymorphisms (SNPs) covering the PON genes were genotyped for statistical analysis. Two of the 11 SNPs (rs662 and rs854560) were contextualized in a meta-analysis of ischemic stroke. Results The presence of rs705381 (−162) in the promoter region of PON1 was significantly associated with total stroke (Padjusted = 0.0007, OR = 0.57 [95% CI = 0.41-0.79]) and ischemic stroke (Padjusted = 0.0017, OR = 0.54 [95% CI = 0.37-0.79]) when analyzed using a dominant model, but was not associated with hemorrhagic stroke. There was also a nominal association between rs854571 (−824) and total stroke. Meta-analysis demonstrated a significant nominal association between rs662 and ischemic stroke, but there was no evidence of an association between rs662 and ischemic stroke risk in a single site association study. Conclusions These findings indicate that polymorphisms of PON1 gene may be a risk factor of stroke.</p